The trial compared rivaroxaban with placebo in more than 5,000 patients with significant coronary artery disease (CAD) and reduced left ventricular ejection fraction (LVEF; ≤40%) following an episode of decompensated chronic HF. Prof. Zannad points out that, “Rivaroxaban is approved at higher doses to treat conditions such as atrial fibrillation (AF) and venous thromboembolism, but in COMMANDER HF, patients were randomised to a lower dose (2.5 mg twice daily) or matching placebo, in combination with antiplatelet therapy and standard therapy for HF.” The primary efficacy endpoint was a composite of all-cause mortality, myocardial infarction (MI) and stroke, and the primary safety endpoint was a composite of fatal bleeding or bleeding into a critical space with potential for permanent disability. Regarding patient baseline characteristics, the median age was 66 years, the majority of patients were men (77%) and median LVEF was 34%.

Prof. Zannad explains the main findings, “During a median follow-up of 21.1 months, we found no significant difference in the primary efficacy outcome, which occurred in 25.0% of patients in the rivaroxaban group compared with 26.2% on placebo (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.84–1.05, p=0.27). There were no differences between groups in all-cause mortality or nonfatal MI but there was a significantly lower rate of nonfatal stroke with rivaroxaban vs placebo (HR 0.66, 95% CI 0.47–0.95, p=0.023).”

“We found no significant difference in the primary efficacy outcome.”

No significant difference in the principal safety outcome was observed, which occurred in 0.7% of patients in the rivaroxaban group and 0.9% in the placebo group (HR 0.80, 95% CI 0.43–1.49, p=0.48); however, patients taking rivaroxaban had a significantly higher risk of International Society on Thrombosis and Haemostasis-defined major bleeding compared with those on placebo (HR 1.68, 95% CI 1.18–2.39, p=0.003).

Prof. Zannad concludes, “The most likely reason rivaroxaban failed to improve the primary efficacy outcome is that thrombin-mediated events are not the major driver of cardiovascular events in patients with recent HF hospitalisation.

ESC Congress is the world’s largest and most influential cardiovascular event contributing to global awareness of the latest clinical trials and breakthrough discoveries. ESC Congress 2018 takes place 25 to 29 August at the Messe München in Munich, Germany. Explore the scientific programme.